Early Online (Volume - 9 | Issue - 1)

Gilbert’s Syndrome Revealed by Hepatotoxicity of Imatinib

Published on: 12th March, 2025

Gilbert’s Syndrome (GS) is a hereditary disease that can cause hyperbilirubinemia due to a mutation in the promoter of the UGT1A1 gene, which causes a decrease in uridine diphosphate glucuronyltransferase enzyme activity. Polymorphisms in the UGT1A1 gene are associated with induced hyperbilirubinemia by Tyrosine Kinase Inhibitors (TKI) in Chronic Myeloid Leukemia (CML). We report a case of patient who developed hepatotoxicity when treated on Imatinib and subsequently diagnosed with Gilbert’s syndrome. Eight months after initiating Imatinib, the patient developed conjunctival jaundice and signs of hepatotoxicity with increase in liver enzymes and hyperbilirubinemia with elevated level of unconjugated bilirubin. Gilbert’s syndrome was suspected in the presence of predominantly unconjugated hyperbilirubinemia and a prior history of transient episodes of jaundice. Genetic testing revealed homozygosity for the UGT1A1 TA7 (*28) polymorphism. Imatinib was stopped due to continuous increase of aminotransferases and hyperbilirubinemia and restarted after improvement of Liver Function Tests (LFTs) with a reduced dose of 200 mg/day but LFTs worsted again, and the patient was switched to Dasatinib 100 mg/day, without hepatic cytolysis and a mild persistent hyperbilirubinemia after a follow up of 20 months.Patients with an unexplained rise in serum bilirubin levels on Imatinib therapy should be screened for the genetic UGT1A1 polymorphisms.
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The Synergistic Effect of Combined Linagliptin and Metformin Improves Hepatic Function in High-fat Diet/Streptozotocin-induced Diabetic Rats

Published on: 2nd June, 2025

Background: Monotherapy for liver dysfunction in diabetes is less effective. This study investigated the effect of combined linagliptin and metformin therapy on liver function in diabetic rats. Methods and materials: Sixty-four matured male (200-300 g) Wistar rats were used. Diabetes was induced with 35 mg/kb.wt streptozotocin injected intraperitoneally. The rats were grouped into eight groups (n = 8). Group I: control; Group II: control + 10 mg/kg body weight linagliptin; Group III: control + 200 mg/kg body weight metformin; Group IV; control + 10 mg/kg body weight linagliptin + 200 mg/kg body weight metformin; Group V: diabetic; Group VI: diabetic + 10 mg/kg body weight linagliptin; Group VII: diabetic + 200 mg/kg body weight metformin; Group VIII: diabetic + 10 mg/kg body weight linagliptin + 200 mg/kg body weight metformin. After the animal was sacrificed, blood and liver samples were collected for biochemical assay. Results: Insulin, blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-cholesterol), liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, pyruvate kinase, glucose-6-phosphatase dehydrogenase, malondialdehyde and inflammatory makers increased (p < 0.05) significantly. High-density lipoprotein-cholesterol (HDL-cholesterol), liver antioxidant, glycogen, and glycogen synthase were reduced significantly in diabetic rats. Linagliptin and metformin administration single and combined reduced the insulin, blood glucose, glycated hemoglobin, total cholesterol, triglycerides, LDL-cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, pyruvate kinase, glucose-6-phosphatase dehydrogenase, malondialdehyde, inflammatory makers and increased the HDL-cholesterol, liver antioxidant, glycogen and glycogen synthase in diabetic rats.Conclusion: Linagliptin monotherapy alone efficiently controls hyperglycemia and remarkably improves liver functions. Combining linagliptin and metformin could be used as safe and effective therapy for liver dysfunction progression in diabetes.
Cite this ArticleCrossMarkPublonsHarvard Library HOLLISGrowKudosResearchGateBase SearchOAI PMHAcademic MicrosoftScilitSemantic ScholarUniversite de ParisUW LibrariesSJSU King LibrarySJSU King LibraryNUS LibraryMcGillDET KGL BIBLiOTEKJCU DiscoveryUniversidad De LimaWorldCatVU on WorldCat
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